Lasix for the prevention of de novo postpartum hypertension: A randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit to oral loop-diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension OBJECTIVE: To evaluate whether oral furosemide can reduce risk for de novo postpartum hypertension (dnPPHTN) among high-risk birthing people by reducing post-delivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for dnPPHTN at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high-risk for the development of dnPPHTN based on a pre-specified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a five-day course of oral furosemide 20 mg daily or identical-appearing placebo starting within eight hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was the difference in mean arterial pressure (MAP) averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation. The study was powered to detect a 5 mmHg difference in mean MAP (standard deviation 6.4 mmHg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of dnPPHTN, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between groups. There was no significant difference in mean MAP 24 hours prior to discharge (or antihypertensive initiation) in the furosemide group (88.9 ± 7.4 mmHg) compared to the placebo group (86.8 ± 7.1 mmHg; absolute difference 2.1 mmHg, 95% CI -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed dnPPHTN and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between groups. CONCLUSIONS: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces mean MAP in the 24 hours prior to discharge from the delivery hospitalization (or antihypertensive medication initiation) compared to placebo.

Vascular type 1 angiotensin receptors control blood pressure by augmenting peripheral vascular resistance in female mice.

Angiotensin II (ANG II) is a major mediator of hypertension pathogenesis. In addition, there are well-documented differences in expression of the renin-angiotensin system (RAS) components and ANG II responses between males and females, which may explain sex differences in blood pressure (BP) and hypertension epidemiology. We previously showed that type 1A angiotensin (AT1A) receptors in vascular smooth muscle cells (VSMCs) play a critical role in BP regulation and hypertension pathogenesis, but these studies were carried out in male mice. Therefore, the major goal of the current studies was to examine the impact of VSMC AT1A receptors on BP and hypertension pathogenesis in female mice. We found that elimination of VSMC AT1A receptors in female mice reduced (≈8 mmHg) baseline BP without altering sodium sensitivity. The severity of ANG II-induced hypertension was diminished (≈33% reduction in BP), particularly during the last 2 wk of chronic ANG II infusion, compared with controls, but natriuresis was not altered during the first 5 days of ANG II infusion. Urinary norepinephrine levels were enhanced in female SMKO compared with control mice. There was a virtually complete elimination of ANG II-induced kidney hemodynamic responses with attenuation of acute vasoconstrictor responses in the systemic vasculature. These findings demonstrate that direct vascular actions of AT1A receptors play a prominent role in BP control and hypertension pathogenesis in female mice.

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control.

Effect of continuous post-operative lidocaine infusion in an enhanced recovery program on opioid use following gynecologic oncology surgery.

OBJECTIVE: To determine the effectiveness of implementing an Enhanced Recovery After Surgery (ERAS) program, including continuous intraoperative and postoperative intravenous (IV) lidocaine infusion, on perioperative opioid use. METHODS: This was a single-institution retrospective pre- post- cohort study. Consecutive patients undergoing planned laparotomy for known or potential gynecologic malignancy were identified after implementation of an ERAS program and compared to a historical cohort. Opioid use was calculated as morphine milligram equivalents (MMEs). Cohorts were compared using bivariate tests. RESULTS: A total of 215 patients were included in the final analysis, 101 patients received surgery before ERAS implementation and 114 received surgery after. A reduction in total opioid use was observed in ERAS patients compared with historical controls (MME 26.5 [9.6-60.8] versus 194.5 [123.8-266.8], p<0.001). Length of stay (LOS) was reduced by 25% in the ERAS cohort (median 3 days, range 2-26, versus 4 days, range 2-18; p<0.001). Within the ERAS cohort, 64.9% received IV lidocaine for the planned 48 hours, and 5.6% had the infusion discontinued early. Within the ERAS cohort, patients who received IV lidocaine infusion used less opioids compared to those who did not (median 16.9, range 5.6-55.1, versus 46.2, range 23.2-76.1; p<0.002). CONCLUSION: An ERAS program including a continuous IV lidocaine infusion as the opioid-sparing analgesic strategy was noted to be safe and effective, leading to decreased opioid consumption and LOS compared with a historic cohort. Additionally, lidocaine infusion was noted to decrease opioid consumption even among patients already receiving other ERAS interventions.

Odontoid fracture type and angulation affect nonunion risk, but comminution and displacement do not: A propensity score matched analysis of fracture morphology.

OBJECTIVE: Odontoid fractures disproportionately affect older patients who have high surgical risk, but also high rates of fracture nonunion. To guide surgical decision-making, we quantified the effect of fracture morphology on nonunion among nonoperatively managed, traumatic, isolated odontoid fractures. METHODS: We examined all patients with isolated odontoid fractures treated nonoperatively at our institution between 2010 and 2019. Multivariable regression and propensity score matching were used to quantify the effect of fracture type, angulation, comminution, and displacement on bony healing by 26 weeks from injury. RESULTS: 303 consecutive traumatic odontoid fracture patients were identified, of whom 163 (53.8 %) had isolated fractures that were managed nonoperatively. Selection for nonoperative management was more likely with older age (OR=1.31 [1.09, 1.58], p = 0.004), and less likely with higher fracture angle (OR=0.70 [0.55, 0.89], p = 0.004), or higher presenting Nurick scores (OR=0.77 [0.62, 0.94], p = 0.011). Factors associated with nonunion at 26 weeks were fracture angle (OR=5.11 [1.43, 18.26], p = 0.012) and Anderson-D'Alonzo Type II morphology (OR=5.79 [1.88, 17.83], p = 0.002). Propensity score matching to assess the effect of type II fracture, fracture angulation> 10o, displacement≥ 3 mm, and comminution all yielded balanced models (Rubin's B<25.0, 0.5  10o (p = 0.015), and there was an 18.2 % lower rate of bony healing for each 10o increase in fracture angle. Fracture displacement≥ 3 mm and comminution had no significant effect. CONCLUSION: Type II fracture morphology and fracture angle > 10o significantly increase nonunion among nonoperatively managed isolated traumatic odontoid fractures, but fracture comminution and displacement ≥ 3 mm do not.

Surgery Decreases Nonunion, Myelopathy, and Mortality for Patients With Traumatic Odontoid Fractures: A Propensity Score Matched Analysis.

BACKGROUND: Existing literature suggests that surgical intervention for odontoid fractures is beneficial but often does not control for known confounding factors. OBJECTIVE: To examine the effect of surgical fixation on myelopathy, fracture nonunion, and mortality after traumatic odontoid fractures. METHODS: We analyzed all traumatic odontoid fractures managed at our institution between 2010 and 2020. Ordinal multivariable logistic regression was used to identify factors associated with myelopathy severity at follow-up. Propensity score analysis was used to test the treatment effect of surgery on nonunion and mortality. RESULTS: Three hundred and three patients with traumatic odontoid fracture were identified, of whom 21.6% underwent surgical stabilization. After propensity score matching, populations were well balanced across all analyses (Rubin's B < 25.0, 0.5 < Rubin's R < 2.0). Controlling for age and fracture angulation, type, comminution, and displacement, the overall rate of nonunion was lower in the surgical group (39.7% vs 57.3%, average treatment effect [ATE] = -0.153 [-0.279, -0.028], P = .017). Controlling for age, sex, Nurick score, Charlson Comorbidity Index, Injury Severity Score, and selection for intensive care unit admission, the mortality rate was lower for the surgical group at 30 days (1.7% vs 13.8%, ATE = -0.101 [-0.172, -0.030], P = .005) and at 1 year was 7.0% vs 23.7%, ATE = -0.099 [-0.181, -0.017], P = .018. Cox proportional hazards analysis also demonstrated a mortality benefit for surgery (hazard ratio = 0.587 [0.426, 0.799], P = .0009). Patients who underwent surgery were less likely to have worse myelopathy scores at follow-up (odds ratio = 0.48 [0.25, 0.93], P = .029). CONCLUSION: Surgical stabilization is associated with better myelopathy scores at follow-up and causes lower rates of fracture nonunion, 30-day mortality, and 1-year mortality.

Peripartum cardiomyopathy delivery hospitalization and postpartum readmission trends, risk factors, and outcomes.

OBJECTIVE: To evaluate risk for peripartum cardiomyopathy during delivery and postpartum hospitalizations, and analyze associated trends, risk factors, and clinical outcomes. METHODS: The 2010-2020 Nationwide Readmissions Database was used for this retrospective cohort study. Delivery hospitalizations along with postpartum readmissions occurring within five months of delivery discharge were analyzed. Risk factors associated with peripartum cardiomyopathy were analyzed with unadjusted and adjusted logistic regression models with odds ratios as measures of effect. Risk for severe adverse outcomes associated with peripartum cardiomyopathy was analyzed. Trends were analyzed with joinpoint regression. RESULTS: Of 39,790,772 delivery hospitalizations identified, 9,210 were complicated by a diagnosis of peripartum cardiomyopathy (2.3 per 10,000). Risk for a 5-month readmission with a peripartum cardiomyopathy diagnosis was 4.8 per 10,000. Factors associated with peripartum cardiomyopathy during deliveries included preeclampsia with severe features (OR 18.9, 95 % CI 17.2, 20.7), preeclampsia without severe features (OR 6.9, 95 % CI 6.1, 7.8), multiple gestation (OR 4.7, 95 % CI 4.1, 5.3), chronic hypertension (OR 10.1, 95 % CI 8.9, 11.3), and older maternal age. Associations were attenuated but retained significance in adjusted models. Similar estimates were found when evaluating associations with postpartum readmissions. Peripartum cardiomyopathy readmissions were associated with 10 % of overall postpartum deaths, 21 % of cardiac arrest/ventricular fibrillation diagnoses, 18 % of extracorporeal membrane oxygenation cases, and 40 % of cardiogenic shock. In joinpoint analysis, peripartum cardiomyopathy increased significantly during delivery hospitalizations (average annual percent change [AAPC] 2.2 %, 95 % CI 1.0 %, 3.4 %) but not postpartum readmissions (AAPC 0.0 %, 95 % CI -1.6 %, 1.6 %). CONCLUSION: Risk for peripartum cardiomyopathy increased during delivery hospitalizations over the study period. Obstetric conditions such as preeclampsia and chronic medical conditions that are increasing in prevalence in the obstetric population were associated with the highest odds of peripartum cardiomyopathy.

Outcomes associated with peripartum hysterectomy in the setting of placenta accreta spectrum disorder.

BACKGROUND: Although peripartum hysterectomy for placenta accreta spectrum disorder is known to be associated with complications at the time of delivery, there are limited data on postpartum outcomes and readmission risk in this population. OBJECTIVE: This study aimed to analyze risks for adverse outcomes and postpartum readmissions in the setting of peripartum hysterectomy for placenta accreta spectrum disorder by severity of placenta accreta spectrum disorder subcategory. STUDY DESIGN: Using the 2016-2020 Nationwide Readmissions Database, this retrospective cohort study identified peripartum hysterectomies with a diagnosis of placenta accreta spectrum disorder. The primary exposure was placenta accreta spectrum disorder, subcategorized as placenta accreta vs increta/percreta. The primary outcome was readmission rate and delivery complications. Complications evaluated included the following: (1) nontransfusion severe maternal morbidity (ntSMM), (2) venous thromboembolism, (3) reoperation, (4) intraoperative complications, (5) hemorrhage, (6) sepsis, and (7) surgical site complications. We additionally evaluated delivery hospitalization and readmission mean length of stay, and hospital costs. Unadjusted and adjusted logistic regression models were fit for outcomes adjusting for clinical, demographic, and hospital factors. The association measures were expressed as unadjusted and adjusted odds ratios with 95% confidence intervals. RESULTS: Between 2016 and 2020, 7864 hysterectomies during a delivery hospitalization with a diagnosis of placenta accreta spectrum disorder were identified (66.5% with placenta accreta and 33.5% with placenta increta/percreta diagnoses). The overall 60-day all-cause readmission rate was 7.3%. Most readmissions (57.2%) occurred within 10 days of hospital discharge. Compared with peripartum hysterectomy with a diagnosis of placenta accreta, hysterectomies with placenta increta/percreta diagnoses carried significantly increased risk of 60-day readmission (adjusted odds ratio, 1.31; 95% confidence interval, 1.01-1.71), inpatient mortality (odds ratio, 13.23; 95% confidence interval, 3.35-52.30), nontransfusion severe maternal morbidity (adjusted odds ratio, 1.43; 95% confidence interval, 1.20-1.71), intraoperative complications (adjusted odds ratio, 2.31; 95% confidence interval, 1.93-2.77), and surgical site complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.23-1.95). The median length of stay during delivery hospitalization was longer for placenta increta/percreta (5.8 days; 95% confidence interval, 5.4-6.1) than for placenta accreta (4.2 days; 95% confidence interval, 4.1-4.3; P<.05). In addition, delivery hospitalization costs were higher in cases of placenta increta/percreta (median, $30,686; 95% confidence interval, $28,922-$32,449) than placenta accreta (median, $21,321; 95% confidence interval, $20,480-$22,163). CONCLUSION: Complication and readmission risks after peripartum hysterectomy with placenta accreta spectrum disorder are high. Compared with patients with placenta accreta, patients with placenta increta/percreta had increased risk for delivery and postoperative complications and postpartum readmission, and increased costs and length of stay.

Maternal vs Fetal Origin of Placental Intervillous Thrombi.

OBJECTIVES: To determine maternal vs fetal origin for blood in placental intervillous thrombi (IVTs). METHODS: We used comparative analysis of microsatellites (short tandem repeats [STRs]), sex chromosome fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for fetal (ɑ-fetoprotein [AFP]) and maternal (immunoglobulin M [IgM]) serum proteins to distinguish the origin of IVTs. Using an informatics approach, we tested the association between IVTs and fetomaternal hemorrhage (FMH). RESULTS: In 9 of 10 cases, the preponderance of evidence showed that the thrombus was mostly or entirely maternal in origin. In 1 case, the thrombus was of mixed origins. STR testing was prone to contamination by entrapped fetal villi. FISH was useful but limited only to cases with male fetuses. IgM showed stronger staining than AFP in 9 cases, supporting maternal origin. By informatics, we found no association between IVTs and FMH. CONCLUSIONS: Evidence supports a maternal origin for blood in IVTs. IHC for IgM and AFP may be clinically useful in determining maternal vs fetal contribution to IVTs.

Single Center Experience with Incidence, Impact and Predictors of Biliary Complications in Donation After Circulatory Death Liver Transplantation.

Introduction: Utilizing allografts from donors after cardiac death (DCD) has improved organ availability, and DCD livers comprise a growing proportion of transplantations. However, it has been suggested that DCD transplantations have worse outcomes. Research Questions: We aimed to characterize outcomes in a large cohort of DCD transplantations, identify trends in outcomes over time, and identify factors associated with the development of biliary complications. Design: We conducted an observational retrospective cohort study of patients receiving DCD liver allografts within a large academic teaching hospital with a high transplantation volume. Consecutive patients who underwent Type III DCD liver transplantation from 2006-2016 were included in our cohort. Re-transplantations and multi-organ transplant recipients were excluded. Results: Ninety-six type III DCD transplantations occurred between 2006-2016. We report a 1one-year patient survival of 90.6% (87) and a 5five-year patient survival of 69.8% (67). Twenty-nine (30.2%) patients experienced any biliary complication in the first year following discharge, with 17 (17.7%) experiencing ischemic cholangiopathy. Five-year patient (P = 0.04) and graft (P = 0.005) survival improved over time. Post-operative biliary complications experienced during index admission and prior to discharge were found to be associated with the development of biliary complications (P = 0.005) and ischemic cholangiopathy (P = 0.01) following discharge. Conclusion: Our data suggested that outcomes using DCD allografts have improved, however biliary complications remain a significant issue in DCD transplantation. Patients who experienced post-operative biliary complications during index admission may require more frequent screening to allow the initiation of earlier treatment for biliary complications.

Concomitant cervical spine fractures are the primary driver of disability after traumatic vertebral artery dissection: A Case series of 123 patients.

Background: Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. Aims and Objectives: To characterize the tVAD population and identify factors associated with clinical outcomes. Materials and Methods: We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Results: Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p<0.0007), were more likely to smoke (OR 3.0 [1.2178, 7.4028], p=0.0202), be male (OR 7.125 [3.0181, 16.8236], p<0.0001), and have mRS≥3 at discharge (OR 3.0545 [1.0937, 8.5752], p=0.0449). On multivariable regression, only fracture independently predicted mRS≥3 at discharge (OR 5.6898 [1.5067, 21.4876], p=0.010). Conclusion: tVADs may be associated with stroke and/or cervical fracture. Presenting symptoms predict stroke, but baseline demographic and clinical characteristics do not. Comorbid cervical fractures, not stroke, drive negative outcomes.

Vertebral Artery Dissections With Concurrent Intracranial Hemorrhage: A Case Series of 13 Patients Among a Cohort of 301.

BACKGROUND: Vertebral artery dissections (VADs) are a rare cause of ischemic stroke that can occasionally lead to intracranial hemorrhage (ICH). This study aims to identify differences in predisposing factors, event characteristics, and outcomes between patients with only a VAD and patients with VAD and concomitant ICH. METHODS: We conducted a retrospective chart review of 301 patients who presented with VADs at our institution from 2004-2018. A total of 13 patients were identified with VAD and concomitant ICH. Data were collected on demographics, event characteristics, treatments, and neurologic outcomes, measured using the modified Rankin Scale (mRS). RESULTS: VAD+ICH and VAD-only groups were similar in terms of age, sex, and recorded comorbidities. Additionally, etiology of the dissections did not seem to vary between groups (P = 0.6), even when selecting for traumatic causes such as motor vehicle accidents (P = 0.22) and violence (P = 0.25). Concomitant strokes and aneurysms/pseudoaneurysms occurred in similar proportions as well, but cervical fractures were more common in the VAD+ICH group (P = 0.003). Using the mRS as a measure of neurological outcome, we found that the VAD+ICH group had worse neurologic function at discharge, 3-month follow-up, and last follow-up (P < 0.001). CONCLUSIONS: Patients who experienced an ICH in addition to a VAD did not have any identifiable risk factors. Cervical spine fractures were more common in patients with VAD and ICH. VAD patients with a concomitant ICH have worse neurologic outcomes than patients with only a VAD.

Characteristics and Predictors of Outcome of Pseudoaneurysms Associated With Vertebral Artery Dissections: A 310-Patient Case Series.

BACKGROUND: Vertebral artery dissections (VADs) are a common cause of stroke in young patients and can result in various secondary effects, including pseudoaneurysm formation. OBJECTIVE: To identify differences in predisposing factors and outcomes for VADs with and without concomitant pseudoaneurysms. METHODS: We retrospective chart reviewed patients who presented to our institution at the time of VAD with at least a 3-mo clinical follow-up. Demographics, VAD characteristics, treatment, and outcomes represented as modified Rankin scale (mRS) scores were collected. RESULTS: Of 310 patients with a VAD included in this study, 301 patients had an identified pseudoaneurysm status, with 54 pseudoaneurysm-associated VADs and 247 VADs not associated with pseudoaneurysm. VAD patients with associated pseudoaneurysms were more likely to be female (P < .004), have bilateral VADs (P < .001), and have fewer vertebral artery segments affected (P = .018), and less likely to have stroke (P < .008) or occlusion of the vertebral artery (P < .001). There was no difference in the proportion of patients treated with antiplatelet agents (P = .12) or anticoagulants (P = .27) between the groups. VAD patients with associated pseudoaneurysms were more likely to have a higher mRS at 3-mo follow-up (P = .044) but not discharge (P = .18) or last follow-up (P = .05). VAD patients with pseudoaneurysms were equally likely to have resolution of occlusion (P = .40) and stenosis (P = .19). CONCLUSION: Demographics and clinical and radiological characteristics of VADs associated with pseudoaneurysms are different from those without associated pseudoaneurysms. Vertebral artery dissections with concomitant pseudoaneurysms are neither associated with worse functional nor radiographic outcomes.

Traumatic and Spontaneous Vertebral Artery Dissections: An Analysis of Tertiary-Center 310 Patient Cohort.

BACKGROUND: Vertebral artery dissections (VADs) are rare yet potentially devastating events. While the etiology of these events is either traumatic or spontaneous, there is a paucity of quantitative literature comparing the two. OBJECTIVE: To identify differences in predisposing factors, event characteristics, and clinical outcomes between traumatic VADs (tVADs) and spontaneous VADs (sVADs). METHODS: We retrospectively identified patients with VADs presenting to our institution at VAD onset with at least a 3-mo follow-up. Demographics, event characteristics, treatment details, and neurological outcomes as modified Rankin scale (mRS) scores were collected. RESULTS: Of the 310 patients sustaining 366 VADs total, 187 (60.3%) patients experienced a total of 221 (60.4%) sVADs and 123 (39.7%) patients experienced a total of 145 (39.6%) tVADs. sVADs were more likely to occur in the intracranial course of the artery (P = .042) and have a lower mRS at discharge, 3-month, and last clinical follow-up (P = 003, .002, and .001, respectively). tVADs were more likely associated with concomitant fractures (P < .001). CONCLUSION: Despite similar patient populations, tVADs are associated with higher mRS scores at all time points. Although further study is needed, this may suggest other concomitant trauma rather than the VAD itself is contributing to worse neurological status in patients with tVADs.

Clinical Characteristics, Course, and Outcomes of Vertebral Artery Dissections in the Postpartum Period.

BACKGROUND: Postpartum vertebral artery dissections (ppVADs) are rare but potentially morbid conditions that occur in otherwise healthy patients. OBJECTIVE: To evaluate clinical characteristics of ppVADs. METHODS: Demographic, clinical, treatment, and outcome data were collected on ppVADs and are presented in a case series of 12 patients and compared to the general cohort. RESULTS: In total, 12 patients had ppVADs in our cohort of 310 patients with vertebral artery dissections (VADs). They occurred 11.27 days (95% CI, -0.85 to 23.39) postdelivery. Of these, there were 5 (42%) with a hypertensive disorder of pregnancy, and 4 (33%) who had migraines. A total of 3 (25%) had ischemic strokes and 1 (8%) had a subarachnoid hemorrhage. In total, 2 patients (17%) had unfavorable modified Rankin Scale (mRS, 2-6) at discharge from hospital. Patients with ppVADs more often had bilateral VADs (42% vs 17%, P = .03), had pseudoaneurysms (50% vs 18%, P = .0068), were younger (33.83 years vs 44.32 years, P = .018), and had lower Charlson Comorbidity Index (CCI = 0 vs 0.99, P = .0038). Anticoagulant treatment was used in a similar percentage of patients. Multivariate analysis revealed 3 factors were predictive of change in mRS: CCI (OR = 1.09, 95% CI, 1.02-1.15), stroke (OR = 0.78, 95% CI, 0.65-0.95), and mRS at hospital discharge (OR = 0.80, 95% CI, 0.74-0.87). CONCLUSION: There are only 15 isolated ppVADs reported in the literature; this study adds 12 patients with 17 ppVADs. Postpartum VADs occur in younger, healthier patients than in the general cohort, raising questions about mechanism of injury. The majority of ppVADs have good neurological outcomes.

Chiropractic associated vertebral artery dissection: An analysis of 34 patients amongst a cohort of 310.

BACKGROUND: Vertebral artery dissections (VAD) are a rare but important cause of ischemic stroke, especially in younger patients. Many etiologies have been identified, including MVAs, cervical fractures, falls, physical exercise, and cervical chiropractic manipulation. The goal of this study was to investigate the subgroup of patients who suffered a chiropractor-associated injury and determine how their prognosis compared to other-cause VAD. METHODS: We conducted a retrospective chart review of 310 patients with vertebral artery dissections who presented at our institution between January 2004 and December 2018. Variables included demographic data, event characteristics, treatment, radiographic outcomes, and clinical outcomes measured using the modified Rankin Scale. FINDINGS: Overall, 34 out of our 310 patients suffered a chiropractor-associated injury. These patients tended to be younger (p = 0.01), female (p = 0.003), and have fewer comorbidities (p = 0.005) compared to patients with other-cause VADs. The characteristics of the injuries were similar, but chiropractor-associated injuries appeared to be milder at discharge and at follow-up. A higher proportion of the chiropractor-associated group had injuries in the 0-2 mRS range at discharge and at 3 months (p = 0.05, p = 0.04) and no patients suffered severe long-term neurologic consequences or death (0% vs. 9.8%, p = 0.05). However, when a multivariate binomial regression was performed, these effects dissipated and the only independent predictor of a worse injury at discharge was the presence of a cervical spine fracture (p < 0.001). INTERPRETATION: Chiropractor-associated injuries are similar to VADs of other causes, and apparent differences in the severity of the injury are likely due to demographic differences between the two populations.

Placental pathology in COVID-19.

OBJECTIVES: To describe histopathologic findings in the placentas of women with COVID-19 during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020 and May 5, 2020 were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: 16 placentas from patients with SARS-CoV-2 were examined (15 with live birth in the 3rd trimester 1 delivered in the 2nd trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), including abnormal or injured maternal vessels, as well as delayed villous maturation, chorangiosis, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of features of maternal vascular malperfusion (MVM), a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

Placental Pathology in COVID-19.

OBJECTIVES: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

Vertebral artery dissections with and without cervical spine fractures: Analysis of 291 patients.

OBJECTIVES: Vertebral artery dissections occur when tears in the intimal layer of the vertebral artery and are associated with trauma, infection, and spontaneous etiologies. We aimed to identify differences in predisposing factors and outcomes in vertebral artery dissections associated with cervical spine fractures compared to those not associated with cervical spine fractures. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with vertebral artery dissections who presented to our institution at the time of dissection and had a minimum of 3 month follow-up and collected data on demographics, event characteristics, treatments, and outcomes in the form of modified Rankin scale scores. RESULTS: In total, 291 patients with VAD were included in this study. Thirty-nine patients with VADs had associated fracture, while 252 patients had VADs without fracture. VAD patients with associated cervical fractures were more likely to be male (p < 0.001), have a greater number of comorbid conditions (p < 0.01), be smokers (p = 0.045), or have violence (p < 0.001) or motor vehicle accidents (p < 0.001) as the cause of their VADs. VAD patients with associated cervical fractures were less likely to have associated aneurysms or pseudoaneurysms (p = 0.002). VAD patients with associated cervical fractures were more likely to have higher mRS at discharge from the hospital (p < 0.001), 3 month follow-up (p < 0.001), and last follow-up (p < 0.001). CONCLUSION: Cervical spine fracture is likely the primary driver of poor neurological outcomes following vertebral artery dissection with associated cervical spine fracture.

Child Access Prevention Firearm Laws and Firearm Fatalities Among Children Aged 0 to 14 Years, 1991-2016.

Importance: Firearms caused more than 500 pediatric fatalities in 2017-a 50% increase from 2009. Laws regulating firearms are one approach to reducing pediatric firearm fatalities. Objective: To evaluate the association between state child access prevention (CAP) firearm laws and pediatric firearm fatalities. Design, Setting, and Participants: A state-level, cross-sectional study of CAP firearm laws throughout the United States, 1991-2016, was conducted using negative binomial regression to analyze differences in state fatality rates in children aged 0 to 14 years. Data analysis was performed from November 21, 2018, to October 18, 2019. Exposures: Implementation of 2 categories of state CAP firearm laws: recklessness laws, which pertain to providing a firearm to a child, and negligence laws, which pertain to accessibility of a firearm within the home. Main Outcomes and Measures: Rates of firearm fatalities across all intents and by specific intent (homicide, suicide, and unintentional) per 100 000 children aged 0 to 14 years. Results: Twenty-five states passed CAP laws between 1989 and 2000. Between 1991 and 2016, 13 697 firearm fatalities occurred in children aged 0 to 14 years. Recklessness laws were not associated with changes in pediatric firearm fatality rates. Negligence laws overall were associated with significant reductions in firearm fatalities in children aged 0 to 14 years, with a 13% relative reduction in all firearm fatalities (95% CI, -18% to -7%), a 15% relative reduction in firearm homicides (95% CI, -22% to -7%), a 12% relative reduction in firearm suicides (95% CI, -20% to -2%), and a 13% relative reduction in unintentional firearm fatalities (95% CI, -24% to -1%). The most stringent negligence laws were associated with unintentional firearm fatality reductions of 59% (95% CI, -68% to -49%). A total of 3929 deaths (29% of all firearm deaths) were associated with states not having passed the most stringent form of negligence CAP laws. Conclusions and Relevance: In this study, negligence laws were associated with relative reductions in firearm fatality rates in children aged 0 to 14 years. The most stringent negligence laws were associated with the largest reductions in unintentional firearm fatalities. Recklessness laws were not associated with reduced firearm fatality rates. The passage of negligence CAP laws may have the potential to reduce firearm fatalities in children.